Physical Medicine and Rehabilitation for Charcot-Marie-Tooth Disease Treatment & Management
- Author: Divakara Kedlaya, MBBS; Chief Editor: Robert H Meier, III, MD more...
Daily heel-cord stretching exercises are desirable to prevent Achilles tendon shortening. Special shoes with good ankle support may be needed. Physical therapy can assist with ambulation and provide necessary evaluation and training with orthoses, such as an ankle-foot orthosis (AFO).
Patients often require an AFO to correct foot drop and to aid walking. It is important to address the biomechanical needs of a CMT patient, since there may be bilateral strength differences due to progression of the disease. Optimizing the mechanical characteristics of the AFO to patient needs can be challenging. One strategy is to design AFOs of varying stiffness and allow patients to experience range energy storage and release characteristics prior to selecting the stiffness they prefer.
Patients with CMT discard AFOs because they highlight their disability, are not essential for their limited daily walking, and are uncomfortable. Prescription of AFOs should be accompanied with psychological support, noting that research of more comfortable and cosmetically acceptable solutions for the problem of footdrop in CMT is ongoing.
Patients with CMT who regularly wore AFOs were more severely affected, had a slower maximum walking speed, higher energy cost of walking, and worse perceived walking ability.
Custom carbon-fiber composite AFOs have been reported to improve gait of CMT patients AFO prescription appears relevant for improving balance and gait performance in CMT patients, particularly when the model adequately compensates for specific muscle deficits. Custom polypropylene AFOs have shown to improve walking speed and gait parameters in patients with CMT.[63, 64]
Transcutaneous electrical nerve stimulator (TENS) units can be used to improve muscle functions in patients with CMT.
Some patients require the use of forearm crutches or a cane for improved gait stability, but fewer than 5% of patients need wheelchairs. Advise patients with Charcot-Marie-Tooth disease (CMT) about weight management, because obesity makes ambulation more difficult. Encourage exercise within each individual patient's capability. Most patients with CMT usually remain physically active.
A literature review by Sman et al suggested that even though studies have shown exercise-related strength and function changes in patients with CMT, these results should be considered cautiously since few such studies are available and their quality of evidence is only moderate.
An occupational therapist may recommend the use of adaptive equipment for activities of daily living (ADL) and self-care. Fitting of a proper orthosis and keeping the wrist and hand in functional position may be required. Vocational and avocational training regarding the importance of career and employment implications may be needed because of persistent weakness of the hands and/or feet.[23, 24]
In Charcot-Marie-Tooth disease (CMT), no treatment currently exists to reverse or slow the natural disease process for the underlying disorder. Nothing can correct the abnormal myelin, prevent the myelin's degeneration, or prevent axonal degeneration.
Stem-cell and gene-transfer therapies are the most promising forms of treatment for the cure of CMT. Some promising results have been reported for antiprogesterone therapy and ascorbic acid treatment for CMT-1A in animal CMT-1A models. Progesterone-receptor antagonists have reduced PMP-22 overexpression and clinical severity in a CMT-1A rat model. Furthermore, ascorbic acid treatment reduced premature death and demyelination in a CMT-1A mouse model. (A literature review by Gess et al, however, suggested that ascorbic acid does not improve outcomes in adults with CMT-1A, as measured by the neuropathy score at 12 months. ) There is also the prospect of developing drugs to reduce the effects of PMP-22 overexpression in gene duplications by down-regulation via the promoter. Improved understanding of the genetics and biochemistry of the disorder offers hope for an eventual treatment.
Charcot-Marie-Tooth disease increases the risk for complications during delivery, which is linked to a higher occurrence of emergency interventions during birth.
Patients often are evaluated and managed symptomatically by a team that includes a physiatrist, a neurologist, an orthopedic surgeon, and physical and occupational therapists.
Orthopedic surgery may be required to correct severe pes cavus deformities, scoliosis, and other joint deformities.[16, 71, 72]
Consult a specialist in neurogenetics to order specific genetic tests and proper genetic counseling.
Dyck PJ, Chance P, Lebo RV. Hereditary motor and sensory neuropathies. Dyck PJ, Thomas PK, Griffen JW, et al, eds. Peripheral Neuropathy. 3rd ed. Saunders; 1993. 1094-136.
Dyck PJ, Karnes JL, Lambert EH. Longitudinal study of neuropathic deficits and nerve conduction abnormalities in hereditary motor and sensory neuropathy type 1. Neurology. 1989 Oct. 39(10):1302-8. [Medline].
Anderson TJ, Klugmann M, Thomson CE, et al. Distinct phenotypes associated with increasing dosage of the PLP gene: implications for CMT1A due to PMP22 gene duplication. Ann N Y Acad Sci. 1999 Sep 14. 883:234-46. [Medline].
Marrosu MG, Vaccargiu S, Marrosu G, et al. A novel point mutation in the peripheral myelin protein 22 (PMP22) gene associated with Charcot-Marie-Tooth disease type 1A. Neurology. 1997 Feb. 48(2):489-93. [Medline].
Suter U, Nave KA. Transgenic mouse models of CMT1A and HNPP. Ann N Y Acad Sci. 1999 Sep 14. 883:247-53. [Medline].
Chapon F, Latour P, Diraison P, Schaeffer S, Vandenberghe A. Axonal phenotype of Charcot-Marie-Tooth disease associated with a mutation in the myelin protein zero gene. J Neurol Neurosurg Psychiatry. 1999 Jun. 66(6):779-82. [Medline]. [Full Text].
Nicholson GA. The dominantly inherited motor and sensory neuropathies: clinical and molecular advances. Muscle Nerve. 2006 May. 33(5):589-97. [Medline].
Vance JM. Charcot-Marie-Tooth disease type 2. Ann N Y Acad Sci. 1999 Sep 14. 883:42-6. [Medline].
Marrosu MG, Vaccargiu S, Marrosu G, et al. Charcot-Marie-Tooth disease type 2 associated with mutation of the myelin protein zero gene. Neurology. 1998 May. 50(5):1397-401. [Medline].
A service of the U.S. National Library of Medicine. Genetics Home Reference: Your reference to understanding genetics conditions. Charcot-Marie-Tooth disease. Published: February 25, 2014. Available at http://ghr.nlm.nih.gov/condition/charcot-marie-tooth-disease.
Kurihara S, Adachi Y, Wada K, et al. An epidemiological genetic study of Charcot-Marie-Tooth disease in Western Japan. Neuroepidemiology. 2002 Sep-Oct. 21(5):246-50. [Medline].
Morocutti C, Colazza GB, Soldati G, et al. Charcot-Marie-Tooth disease in Molise, a central-southern region of Italy: an epidemiological study. Neuroepidemiology. 2002 Sep-Oct. 21(5):241-5. [Medline].
Braathen GJ. Genetic epidemiology of Charcot-Marie-Tooth disease. Acta Neurol Scand Suppl. 2012. iv-22. [Medline].
Holmes JR, Hansen ST Jr. Foot and ankle manifestations of Charcot-Marie-Tooth disease. Foot Ankle. 1993 Oct. 14(8):476-86. [Medline].
Burns J, Ryan MM, Ouvrier RA. Evolution of foot and ankle manifestations in children with CMT1A. Muscle Nerve. 2009 Feb. 39(2):158-66. [Medline].
Carter GT, Jensen MP, Galer BS, et al. Neuropathic pain in Charcot-Marie-Tooth disease. Arch Phys Med Rehabil. 1998 Dec. 79(12):1560-4. [Medline].
Garcia CA. A clinical review of Charcot-Marie-Tooth. Ann N Y Acad Sci. 1999 Sep 14. 883:69-76. [Medline].
Thomas PK. Overview of Charcot-Marie-Tooth disease type 1A. Ann N Y Acad Sci. 1999 Sep 14. 883:1-5. [Medline].
Auer-Grumbach M, Wagner K, Strasser-Fuchs S, et al. Clinical predominance of proximal upper limb weakness in CMT1A syndrome. Muscle Nerve. 2000 Aug. 23(8):1243-9. [Medline].
Pareyson D, Taroni F, Botti S, et al. Cranial nerve involvement in CMT disease type 1 due to early growth response 2 gene mutation. Neurology. 2000 Apr 25. 54(8):1696-8. [Medline].
van Pomeren M, Selles RW, van Ginneken BT, et al. The hypothesis of overwork weakness in Charcot-Marie-Tooth: a critical evaluation. J Rehabil Med. 2009 Jan. 41(1):32-4. [Medline].
Burns J, Bray P, Cross LA, et al. Hand involvement in children with Charcot-Marie-Tooth disease type 1A. Neuromuscul Disord. 2008 Dec. 18(12):970-3. [Medline].
Pazzaglia C, Vollono C, Ferraro D, Virdis D, Lupi V, Le Pera D. Mechanisms of neuropathic pain in patients with Charcot-Marie-Tooth 1 A: a laser-evoked potential study. Pain. 2010 May. 149(2):379-85. [Medline].
Ribiere C, Bernardin M, Sacconi S, Delmont E, Fournier-Mehouas M, Rauscent H. Pain assessment in Charcot-Marie-Tooth (CMT) disease. Ann Phys Rehabil Med. 2012 Apr. 55(3):160-73. [Medline].
Kousseff BG, Hadro TA, Treiber DL, et al. Charcot-Marie-Tooth disease with sensorineural hearing loss--an autosomal dominant trait. Birth Defects Orig Artic Ser. 1982. 18(3B):223-8. [Medline].
Stojkovic T, Latour P, Vandenberghe A, et al. Sensorineural deafness in X-linked Charcot-Marie-Tooth disease with connexin 32 mutation (R142Q). Neurology. 1999 Mar 23. 52(5):1010-4. [Medline].
Nelis E, Timmerman V, De Jonghe P, et al. Molecular genetics and biology of inherited peripheral neuropathies: a fast-moving field. Neurogenetics. 1999 Sep. 2(3):137-48. [Medline].
Pareyson D. Charcot-Marie-Tooth disease and related neuropathies: molecular basis for distinction and diagnosis. Muscle Nerve. 1999 Nov. 22(11):1498-509. [Medline].
Bergoffen J, Scherer SS, Wang S, et al. Connexin mutations in X-linked Charcot-Marie-Tooth disease. Science. 1993 Dec 24. 262(5142):2039-42. [Medline].
Bone LJ, Dahl N, Lensch MW, et al. New connexin32 mutations associated with X-linked Charcot-Marie-Tooth disease. Neurology. 1995 Oct. 45(10):1863-6. [Medline].
Lewis RA. The challenge of CMTX and connexin 32 mutations. Muscle Nerve. 2000 Feb. 23(2):147-9. [Medline].
Nicholson SM, Ressot C, Gomes D, et al. Connexin32 in the peripheral nervous system. Functional analysis of mutations associated with X-linked Charcot-Marie-Tooth syndrome and implications for the pathophysiology of the disease. Ann N Y Acad Sci. 1999 Sep 14. 883:168-85. [Medline].
Chance PF. Overview of hereditary neuropathy with liability to pressure palsies. Ann N Y Acad Sci. 1999 Sep 14. 883:14-21. [Medline].
Ionasescu VV, Ionasescu R, Searby C, et al. Dejerine-Sottas disease with de novo dominant point mutation of the PMP22 gene. Neurology. 1995 Sep. 45(9):1766-7. [Medline].
Ben Othmane K, Hentati F, Lennon F, et al. Linkage of a locus (CMT4A) for autosomal recessive Charcot-Marie-Tooth disease to chromosome 8q. Hum Mol Genet. 1993 Oct. 2(10):1625-8. [Medline].
Bolino A, Muglia M, Conforti FL, et al. Charcot-Marie-Tooth type 4B is caused by mutations in the gene encoding myotubularin-related protein-2. Nat Genet. 2000 May. 25(1):17-9. [Medline].
Gambardella A, Bolino A, Muglia M, et al. Genetic heterogeneity in autosomal recessive hereditary motor and sensory neuropathy with focally folded myelin sheaths (CMT4B). Neurology. 1998 Mar. 50(3):799-801. [Medline].
Carter GT, Abresch RT, Fowler WM, et al. Profiles of neuromuscular diseases. Hereditary motor and sensory neuropathy, types I and II. Am J Phys Med Rehabil. 1995 Sep-Oct. 74(5 Suppl):S140-9. [Medline].
Keller MP, Chance PF. Inherited neuropathies: from gene to disease. Brain Pathol. 1999 Apr. 9(2):327-41. [Medline].
Bird TD, Ott J, Giblett ER, et al. Genetic linkage evidence for heterogeneity in Charcot-Marie-Tooth neuropathy (HMSN type I). Ann Neurol. 1983 Dec. 14(6):679-84. [Medline].
Berciano J, Combarros O, Figols J, et al. Hereditary motor and sensory neuropathy type II. Clinicopathological study of a family. Brain. 1986 Oct. 109 ( Pt 5):897-914. [Medline].
Rose KJ, Hiller CE, Mandarakas M, Raymond J, Refshauge K, Burns J. Correlates of functional ankle instability in children and adolescents with Charcot-Marie-Tooth disease. J Foot Ankle Res. 2015. 8:61. [Medline]. [Full Text].
Murphy SM, Laura M, Fawcett K, Pandraud A, Liu YT, Davidson GL. Charcot-Marie-Tooth disease: frequency of genetic subtypes and guidelines for genetic testing. J Neurol Neurosurg Psychiatry. 2012 Jul. 83(7):706-10. [Medline].
Shaffer LG, Kennedy GM, Spikes AS, et al. Diagnosis of CMT1A duplications and HNPP deletions by interphase FISH: implications for testing in the cytogenetics laboratory. Am J Med Genet. 1997 Mar 31. 69(3):325-31. [Medline].
Nicholson GA. Penetrance of the hereditary motor and sensory neuropathy Ia mutation: assessment by nerve conduction studies. Neurology. 1991 Apr. 41(4):547-52. [Medline].
Hayasaka K, Himoro M, Sato W, et al. Charcot-Marie-Tooth neuropathy type 1B is associated with mutations of the myelin P0 gene. Nat Genet. 1993 Sep. 5(1):31-4. [Medline].
Birouk N, LeGuern E, Maisonobe T, et al. X-linked Charcot-Marie-Tooth disease with connexin 32 mutations: clinical and electrophysiologic study. Neurology. 1998 Apr. 50(4):1074-82. [Medline].
Elliott JL, Kwon JM, Goodfellow PJ, et al. Hereditary motor and sensory neuropathy IIB: clinical and electrodiagnostic characteristics. Neurology. 1997 Jan. 48(1):23-8. [Medline].
England JD, Garcia CA. Electrophysiological studies in the different genotypes of Charcot- Marie-Tooth disease. Curr Opin Neurol. 1996 Oct. 9(5):338-42. [Medline].
Gutierrez A, England JD, Sumner AJ, et al. Unusual electrophysiological findings in X-linked dominant Charcot-Marie-Tooth disease. Muscle Nerve. 2000 Feb. 23(2):182-8. [Medline].
Lewis RA, Sumner AJ. Electrophysiologic features of inherited demyelinating neuropathies: a reappraisal. Ann N Y Acad Sci. 1999 Sep 14. 883:321-35. [Medline].
Quattrone A, Gambardella A, Bono F, et al. Autosomal recessive hereditary motor and sensory neuropathy with focally folded myelin sheaths: clinical, electrophysiologic, and genetic aspects of a large family. Neurology. 1996 May. 46(5):1318-24. [Medline].
Nicholson G, Nash J. Intermediate nerve conduction velocities define X-linked Charcot-Marie- Tooth neuropathy families. Neurology. 1993 Dec. 43(12):2558-64. [Medline].
Bornemann A, Hansen FJ, Schmalbruch H. Nerve and muscle biopsy in a case of hereditary motor and sensory neuropathy type III with basal lamina onion bulbs. Neuropathol Appl Neurobiol. 1996 Feb. 22(1):77-81. [Medline].
Guillebastre B, Calmels P, Rougier PR. Assessment of appropriate ankle-foot orthoses models for patients with Charcot-Marie-Tooth disease. Am J Phys Med Rehabil. 2011 Aug. 90(8):619-27. [Medline].
Njegovan ME, Leonard EI, Joseph FB. Rehabilitation medicine approach to Charcot-Marie-Tooth disease. Clin Podiatr Med Surg. 1997 Jan. 14(1):99-116. [Medline].
Vinci P, Gargiulo P. Poor compliance with ankle-foot-orthoses in Charcot-Marie-Tooth disease. Eur J Phys Rehabil Med. 2008 Mar. 44(1):27-31. [Medline].
Ramdharry GM, Pollard AJ, Marsden JF, Reilly MM. Comparing gait performance of people with Charcot-Marie-Tooth disease who do and do not wear ankle foot orthoses. Physiother Res Int. 2012 Dec. 17(4):191-9. [Medline].
Dufek JS, Neumann ES, Hawkins MC, O'Toole B. Functional and dynamic response characteristics of a custom composite ankle foot orthosis for Charcot-Marie-Tooth patients. Gait Posture. 2014 Jan. 39(1):308-13. [Medline].
Guillebastre B, Calmels P, Rougier PR. Assessment of appropriate ankle-foot orthoses models for patients with Charcot-Marie-Tooth disease. Am J Phys Med Rehabil. 2011 Aug. 90(8):619-27. [Medline].
Phillips MF, Robertson Z, Killen B, White B. A pilot study of a crossover trial with randomized use of ankle-foot orthoses for people with Charcot-Marie-tooth disease. Clin Rehabil. 2012 Jun. 26(6):534-44. [Medline].
Hassel B. Improvement of muscle function in Charcot-Marie-Tooth disease by transcutaneous electric nerve stimulation. Muscle Nerve. 1998 Feb. 21(2):267-8. [Medline].
El Mhandi L, Pichot V, Calmels P, Gautheron V, Roche F, Féasson L. Exercise training improves autonomic profiles in patients with Charcot-Marie-Tooth disease. Muscle Nerve. 2011 Nov. 44(5):732-6. [Medline].
Sman AD, Hackett D, Fiatarone Singh M, Fornusek C, Menezes MP, Burns J. Systematic review of exercise for Charcot-Marie-Tooth disease. J Peripher Nerv Syst. 2015 May 22. [Medline].
Gess B, Baets J, De Jonghe P, Reilly MM, Pareyson D, Young P. Ascorbic acid for the treatment of Charcot-Marie-Tooth disease. Cochrane Database Syst Rev. 2015 Dec 11. 12:CD011952. [Medline].
Hoff JM, Gilhus NE, Daltveit AK. Pregnancies and deliveries in patients with Charcot-Marie-Tooth disease. Neurology. 2005 Feb 8. 64(3):459-62. [Medline].
Ward CM, Dolan LA, Bennett DL, et al. Long-term results of reconstruction for treatment of a flexible cavovarus foot in Charcot-Marie-Tooth disease. J Bone Joint Surg Am. 2008 Dec. 90(12):2631-42. [Medline]. [Full Text].
Wukich DK, Bowen JR. A long-term study of triple arthrodesis for correction of pes cavovarus in Charcot-Marie-Tooth disease. J Pediatr Orthop. 1989 Jul-Aug. 9(4):433-7. [Medline].
Graf WD, Chance PF, Lensch MW, et al. Severe vincristine neuropathy in Charcot-Marie-Tooth disease type 1A. Cancer. 1996 Apr 1. 77(7):1356-62. [Medline].
Kuruvilla G, Perry S, Wilson B, et al. The natural history of vincristine-induced laryngeal paralysis in children. Arch Otolaryngol Head Neck Surg. 2009 Jan. 135(1):101-5. [Medline].
Dyck PJ, Swanson CJ, Low PA, et al. Prednisone-responsive hereditary motor and sensory neuropathy. Mayo Clin Proc. 1982 Apr. 57(4):239-46. [Medline].
Sahenk Z, Nagaraja HN, McCracken BS, King WM, Freimer ML, Cedarbaum JM, et al. NT-3 promotes nerve regeneration and sensory improvement in CMT1A mouse models and in patients. Neurology. 2005 Sep 13. 65(5):681-9. [Medline].
Pareyson D, Marchesi C. Natural history and treatment of peripheral inherited neuropathies. Adv Exp Med Biol. 2009. 652:207-24. [Medline].
Passage E, Norreel JC, Noack-Fraissignes P, et al. Ascorbic acid treatment corrects the phenotype of a mouse model of Charcot-Marie-Tooth disease. Nat Med. 2004 Apr. 10(4):396-401. [Medline].
Burns J, Ouvrier RA, Yiu EM, Joseph PD, Kornberg AJ, Fahey MC, et al. Ascorbic acid for Charcot-Marie-Tooth disease type 1A in children: a randomised, double-blind, placebo-controlled, safety and efficacy trial. Lancet Neurol. 2009 Jun. 8(6):537-44. [Medline].
Micallef J, Attarian S, Dubourg O, Gonnaud PM, Hogrel JY, Stojkovic T, et al. Effect of ascorbic acid in patients with Charcot-Marie-Tooth disease type 1A: a multicentre, randomised, double-blind, placebo-controlled trial. Lancet Neurol. 2009 Dec. 8(12):1103-10. [Medline].
Verhamme C, de Haan RJ, Vermeulen M, Baas F, de Visser M, van Schaik IN. Oral high dose ascorbic acid treatment for one year in young CMT1A patients: a randomised, double-blind, placebo-controlled phase II trial. BMC Med. 2009 Nov 12. 7:70. [Medline]. [Full Text].
Pareyson D, Reilly MM, Schenone A, Fabrizi GM, Cavallaro T, Santoro L, et al. Ascorbic acid in Charcot-Marie-Tooth disease type 1A (CMT-TRIAAL and CMT-TRAUK): a double-blind randomised trial. Lancet Neurol. 2011 Apr. 10(4):320-8. [Medline]. [Full Text].
Meyer zu Horste G, Prukop T, Liebetanz D, Mobius W, Nave KA, Sereda MW. Antiprogesterone therapy uncouples axonal loss from demyelination in a transgenic rat model of CMT1A neuropathy. Ann Neurol. 2007 Jan. 61(1):61-72. [Medline].
Sereda MW, Meyer zu Hörste G, Suter U, Uzma N, Nave KA. Therapeutic administration of progesterone antagonist in a model of Charcot-Marie-Tooth disease (CMT-1A). Nat Med. 2003 Dec. 9(12):1533-7. [Medline].
Shy ME. Charcot-Marie-Tooth disease: an update. Curr Opin Neurol. 2004 Oct. 17(5):579-85. [Medline].
Weimer LH, Podwall D. Medication-induced exacerbation of neuropathy in Charcot Marie Tooth disease. J Neurol Sci. 2006 Mar 15. 242(1-2):47-54. [Medline].
Shy ME, Blake J, Krajewski K, et al. Reliability and validity of the CMT neuropathy score as a measure of disability. Neurology. 2005 Apr 12. 64(7):1209-14. [Medline].
Burns J, Ouvrier R, Estilow T, Shy R, Laurá M, Pallant JF, et al. Validation of the Charcot-Marie-Tooth disease pediatric scale as an outcome measure of disability. Ann Neurol. 2012 May. 71(5):642-52. [Medline]. [Full Text].
Siskind CE, Panchal S, Smith CO, Feely SM, Dalton JC, Schindler AB, et al. A review of genetic counseling for Charcot Marie Tooth disease (CMT). J Genet Couns. 2013 Aug. 22(4):422-36. [Medline].
|CMT Type||Chromosome; Inheritance Pattern||Age of Onset||Clinical Features||Average NCVs§|
|CMT-1A (PMP-22¶ dupl.)||17p11.2; AD*||First decade||Distal weakness||15-20 m/s|
|CMT-1B (P0 -MPZ)**||1q23.3; AD||First decade||Distal weakness||< 20 m/s|
|CMT-1C (non-A, non-B) (LITAF)||16p13.13;AD||Second decade||Distal weakness||26-42 m/s|
|CMT-1D (EGR-2)#||10q21.3; AD||First decade||Distal weakness||15-20 m/s|
|CMT-1E (PMP22)||17p11.2; AD||First decade||Distal weakness, deafness||15-20 m/s|
|CMT-1F (NEFL)||8p21.2; AD||First decade||Distal weakness||15-20 m/s|
|CMT-X (connexin-32)[31, 32, 33, 34]||Xq13; XD‡||Second decade||Distal weakness||25-40 m/s|
|CMT-2A||1p36; AD||10 y||Distal weakness||>38 m/s|
|CMT-2B||3q21; AD||Second decade||Distal weakness,
sensory loss, skin ulcers
|Axon loss; Normal|
|CMT-2C||12q23-q24, AD||First decade||Vocal cord, diaphragm, and
|CMT-2D||7p14; AD||16-30 y||Distal weakness, upper limb predominantly||Axon loss; N††|
|CMT-2E||8p21; AD||10-30 y||Distal weakness, lower limb predominantly||Axon loss; N|
|CMT-2F||7q11-q21; AD||15-25 y||Distal weakness||Axon loss; N|
|CMT-2G||12q12-q13; AD||9-76 y||Distal weakness||Axon loss; N|
|CMT-2H||8q21; AD||15-25 y||Distal weakness, pyramidal features||Axon loss; N|
|CMT-2I||1q23; AD||47-60 y||Distal weakness||Axon loss; N|
|CMT-2J||1q23; AD||40-50 y||Distal weakness, hearing loss||Axon loss; N|
|CMT-2K||8q13-q21; AD||< 4 y||Distal weakness||Axon loss; N|
|CMT-2L||12q24; AD||15-25 y||Distal weakness||Axon loss; N|
|CMT–R-Ax (Ouvrier)||AR||First decade||Distal weakness||Axon loss; N|
|CMT–R-Ax (Moroccan)||1q21; AR||Second decade||Distal weakness||Axon loss; N|
|Cowchock syndrome||Xq24-q26||First decade||Distal weakness, deafness, mental retardation||Axon loss; N|
|HNPP|| (PMP-22 deletion)
or tomaculous neuropathy
|17p11; AD||All ages||Episodic weakness and numbness||Conduction Blocks|
|Dejerine-Sottas-syndrome (DSS) or HMSN-3||P0; AR
|2 y||Severe weakness||< 10 m/s|
|P0, EGR-2 or PMP-22
|Birth||Severe weakness||< 10 m/s|
|CMT-4A||8q13; AR||Childhood||Distal weakness||Slow|
protein 2)[38, 39]
|11q23; AR||2-4 y||Distal and proximal
|CMT-4C||5q23; AR||5-15 y||Delayed walking||14-32 m/s|
regulated gene 1)
|8q24; AR||1-10 y||Distal muscle wasting, foot and hand deformities||10-20 m/s|
|CMT-4E (EGR-2)||10q21; AR||Birth||Infant hypotonia||9-20 m/s|
|CMT-4G||10q23.2; AR||8-16 years||Distal weakness||9-20 m/s|
|CMT-4H||12p11.21-q13.11; AR||0-2 years||Delayed walking||9-20 m/s|
|CMT-4F||19q13; AR||1-3 y||Motor delay||Absent|
§Nerve conduction velocities
||Hereditary neuropathy with liability to pressure palsy
¶Peripheral myelin protein
#Early growth response
**Myelin protein zero